etelcalcetide (Rx)

Brand and Other Names:Parsabiv

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injectable solution (single-dose vials)

  • 2.5mg/0.5mL
  • 5mg/mL
  • 10mg/2mL

Secondary Hyperparathyroidism (SHPT)

Indicated for patients with chronic kidney disease (CKD) on hemodialysis

Initial dose

  • Ensure corrected serum calcium is at or above the lower limit of normal prior to initiation, a dose increase, or reinitiation of therapy after a dosing interruption
  • 5 mg IV push 3 times/week at the end of hemodialysis treatment

Maintenance dose

  • Individualize and determine by titration based on parathyroid hormone (PTH) and corrected serum calcium response
  • 2.5 mg IV 3 times/week; titrate dose by 2.5- or 5-mg increments not more frequently than q4Weeks to maintain PTH levels within target range and corrected serum calcium within the normal range; maximum dose of 15 mg 3 times/week

Dosage Modifications

PTH levels below the target range

  • Decrease or temporarily discontinue therapy

Corrected serum calcium below the lower limit of normal (LLN), but ≥7.5 mg/dL (asymptomatic hypocalcemia)

  • Consider decreasing or temporarily discontinuing drug or use concomitant therapies to increase corrected serum calcium
  • If dose is stopped, reinitiate at a lower dose when PTH is within the target range and hypocalcemia has been corrected

Hypocalcemia

  • Stop drug if corrected serum calcium is <7.5 mg/dL or hypocalcemia is symptomatic
  • May reinitiate at a dose 5 mg lower than the last dose administered when corrected serum calcium is within normal limits, symptoms of hypocalcemia have resolved, and predisposing factors for hypocalcemia have been addressed
  • If the last administered dose was 2.5 mg or 5 mg, reinitiate at a dose of 2.5 mg

Switching from cinacalcet

  • Discontinue cinacalcet for at least 7 days before starting etelcalcetide
  • Initiate etelcalcetide at a starting dose of 5 mg IV bolus
  • Ensure corrected serum calcium is at or above the lower limit of normal prior to initiation

Dosing Considerations

Monitoring

  • Monitor corrected serum calcium and PTH levels during dose initiation, dose adjustment, and dose maintenance
  • Corrected serum calcium levels
    • Obtain 1 week after dose initiation or dose adjustment
    • Obtain q4 weeks during maintenance
  • PTH levels
    • Obtain 4 weeks after dose initiation or dose adjustment
    • Obtain per clinical practice during maintenance

Limitations of use

  • Not studied in adults with parathyroid carcinoma, primary hyperparathyroidism, or CKD who are not on hemodialysis
  • Not recommended for use in these populations

Safety and efficacy not established

Hyperparathyroidism (Orphan)

Orphan designation for treatment of pediatric hyperparathyroidism

Sponsor

  • Amgen, Inc; 1 Amgen Center Drive; Thousand Oaks, California 91320

No clinically significant differences in safety, efficacy, or etelcalcetide plasma concentrations were observed between patients ≥65 yr and younger patients

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Interactions

Interaction Checker

and etelcalcetide

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Contraindicated (1)

            • cinacalcet

              cinacalcet, etelcalcetide. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Discontinue cinacalcet for at least 7 days before starting etelcalcetide. Concurrent administration of CaSR agonists could result in severe, life-threatening, hypocalcemia.

            Serious - Use Alternative (0)

              Monitor Closely (0)

                Minor (0)

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                  Adverse Effects

                  >10%

                  Decreased serum calcium, asymptomatic reductions in calcium <7.5 mg/dL or clinically significant asymptomatic reductions in corrected serum calcium between 7.5 and <8.3 mg/dL that required medical management (64%)

                  Muscle spasms (12%)

                  Diarrhea (11%)

                  Nausea (11%)

                  1-10%

                  Vomiting (9%)

                  Headache (8%)

                  Hypocalcemia (7%)

                  Paresthesia (6%)

                  Hypersensitivity (4.4%)

                  Hyperkalemia (4%)

                  Hospitalization for heart failure (2%)

                  Myalgia (2%)

                  QTc prolongation secondary to hypocalcemia (1.2%)

                  Hypophosphatemia (1%)

                  <1%

                  Hypocalcemia, symptomatic reductions in corrected serum calcium <8.3 mg/dL (0.2%)

                  Postmarketing Reports

                  Anaphylactic reaction

                  Seizures secondary to hypocalcemia

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                  Warnings

                  Contraindications

                  Hypersensitivity to etelcalcetide or any of its excipients

                  Cautions

                  Cases of hypotension, congestive heart failure, and decreased myocardial performance reported in clinical trials; reductions in corrected serum calcium may be associated with congestive heart failure, however, a causal relationship could not be completely excluded closely monitor for worsening signs and symptoms of heart failure

                  Adynamic bone may develop if PTH levels are chronically suppressed; if PTH levels decrease below the recommended target range, the dose of vitamin D sterols and/or etelcalcetide should be reduced or discontinued; after discontinuation, resume therapy at a lower dose to maintain PTH levels in the target range

                  Rare reports of upper GI bleeding occurred during clinical trials; the exact cause of the GI bleeds were unknown and there were too few cases to determine if GI bleeding was related to this medication; patients with risk factors for upper GI bleeding (such as known gastritis, esophagitis, ulcers, or severe vomiting) may be at increased risk for GI bleeding while receiving therapy; monitor patients for worsening of common GI adverse reactions of nausea and vomiting associated with this medication and for signs and symptoms of GI bleeding and ulcerations during therapy; promptly evaluate and treat any suspected GI bleeding

                  Hypocalcemia

                  • Etelcalcetide lowers serum calcium and can lead to hypocalcemia, sometimes severe; low serum calcium can cause paresthesias, myalgias, muscle spasms, seizures, QT interval prolongation, and ventricular arrhythmia
                  • Coadministration with another oral calcium-sensing receptor agonist could result in severe, life-threatening hypocalcemia; closely monitor corrected serum calcium in patients receiving etelcalcetide and concomitant therapies known to lower serum calcium
                  • Patients with congenital long QT syndrome, history of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, and other conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to therapy; closely monitor corrected serum calcium and QT interval in patients at risk receiving therapy
                  • Significant reductions in corrected serum calcium may lower threshold for seizures; patients with a history of seizure disorder may be at increased risk for seizures if they develop hypocalcemia due to this medication; monitor corrected serum calcium in patients with seizure disorders receiving therapy

                  • Do not initiate in patients if corrected serum calcium is less than lower limit of normal; monitor corrected serum calcium within 1 week after initiation or dose adjustment and every 4 weeks during treatment; educate patients on symptoms of hypocalcemia and advise them to contact a healthcare provider if they occur

                  • If corrected serum calcium falls below lower limit of normal or symptoms of hypocalcemia develop, start or increase calcium supplementation (including calcium, calcium-containing phosphate binders, and/or vitamin D sterols or increases in dialysate calcium concentration); dose reduction or discontinuation of therapy may be necessary
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                  Pregnancy

                  Pregnancy

                  There are no available data on the use in pregnant women

                  Animal studies

                  • In animal reproduction studies, effects were seen at doses associated with maternal toxicity that included hypocalcemia
                  • In a prenatal and postnatal study in rats administered etelcalcetide during organogenesis through delivery and weaning, there was a slight increase in perinatal pup mortality, delay in parturition, and transient effects on pup growth at exposures 1.8 times the human exposure for the clinical dose of 15 mg 3 times/week

                  Lactation

                  Unknown if distributed in human breast milk

                  Studies in rats showed distribution in milk at concentrations similar to plasma

                  Because of the potential for etelcalcetide to cause adverse effects in breastfed infants, including hypocalcemia, use is not recommended while breastfeeding

                  Pregnancy Categories

                  A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                  B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                  C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                  D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                  X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                  NA: Information not available.

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                  Pharmacology

                  Mechanism of Action

                  Calcimimetic agent that allosterically modulates the calcium-sensing receptor (CaSR)

                  Etelcalcetide binds to the CaSR and enhances activation of the receptor by extracellular calcium

                  Activation of the CaSR on parathyroid chief cells decreases PTH secretion

                  Distribution

                  Protein bound: Predominately bound to plasma albumin by reversible covalent binding

                  Blood to plasma ratio: ~0.6

                  Vd: 796 L

                  Metabolism

                  Biotransformed in blood by reversible disulfide exchange with endogenous thiols to predominantly form conjugates with serum albumin

                  Not metabolized by CYP450 enzymes

                  Elimination

                  Half-life: 3-4 days

                  Excretion

                  • Normal renal function (volunteers in clinical trials): Cleared by renal excretion
                  • Hemodialysis: Removed with a hemodialysis clearance value of 7.66 L/hr
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                  Administration

                  IV Preparation

                  Do not mix or dilute prior to administration

                  Solution is clear and colorless

                  Inspect for particulate matter and discoloration prior to administration

                  Do not use vial if particulate matter or discoloration is observed

                  IV Administration

                  Administer IV push into venous line of the dialysis circuit during rinse back or IV after rinse back; only administer at the end of hemodialysis treatment

                  Administered during rinse back: Administer a sufficient volume of 0.9% NaCl (eg, 150 mL) of rinse back into dialysis tubing

                  Administered after rinse back: Flush line with at least 10 mL of 0.9% NaCl

                  Missed dose

                  • If a regularly scheduled hemodialysis treatment is missed, DO NOT administer any missed doses
                  • Resume dose at the end of the next hemodialysis treatment at the prescribed dose
                  • If doses are missed for >2 weeks, reinitiate at the recommended starting dose of 5 mg (or 2.5 mg if that was the patient’s last dose)

                  Storage

                  Store in the original carton in refrigerator at 2-8°C (36-46°F) to protect from light

                  Once removed from the refrigerator

                  • Do not expose to temperatures >25°C (77°F)
                  • Use within 7 days if stored in the original carton
                  • Use within 4 hr and do not expose to direct sunlight if removed from the original carton
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                  Images

                  BRAND FORM. UNIT PRICE PILL IMAGE
                  Parsabiv intravenous
                  -
                  5 mg/mL vial
                  Parsabiv intravenous
                  -
                  5 mg/mL vial
                  Parsabiv intravenous
                  -
                  5 mg/mL vial
                  Parsabiv intravenous
                  -
                  5 mg/mL vial
                  Parsabiv intravenous
                  -
                  5 mg/mL vial
                  Parsabiv intravenous
                  -
                  5 mg/mL vial

                  Copyright © 2010 First DataBank, Inc.

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                  Patient Handout

                  A Patient Handout is not currently available for this monograph.
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                  Formulary

                  FormularyPatient Discounts

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                  The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                  Tier Description
                  1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                  2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                  3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                  4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  NC NOT COVERED – Drugs that are not covered by the plan.
                  Code Definition
                  PA Prior Authorization
                  Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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                  Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.